PTI-125 for Mild-to-moderate Alzheimer's Disease Patients

• Status: Completed
• Trial end date: 2019-05-08
• Target enrollment: 0
• Participant gender: All

Summary

This is a Phase 2a, multi-center, open-label study of PTI-125 in mild-to-moderate Alzheimer's disease patients.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Pain Therapeutics
• Collaborators: National Institute on Aging (NIA); National Institutes of Health (NIH)

Criteria

Inclusion Criteria:

• Ages >= 50 and <= 85 years

• Informed consent form (ICF) signed by the subject or legally acceptable representative.

• Clinical diagnosis of dementia due to possible or probable Alzheimer's disease

• Mini-Mental State Examination score >= 16 and <= 24 at screening

• If female, postmenopausal for at least 1 year

• Patient living at home, senior residential setting, or an institutional setting without the need for continuous (i.e. 24-hour) nursing care

• General health status acceptable for participation in the study

• Fluency (oral and written) in English or Spanish

• If receiving memantine, rivastigmine, galantamine or an AChEI, receiving a stable dose for at least 3 months (90 days) before screening and with continuous dosing for at least 3 months. If receiving donepezil, receiving any dose lower than 23 mg once daily.

• The patient is a non-smoker for at least 12 months.

• The patient or legal representative must agree to comply with the drawing of blood samples and with a lumbar puncture and the drawing of cerebrospinal fluid samples.

• The patient has a ratio of total tau/Abeta42 in cerebrospinal fluid >= 0.30.

• Patient has a caregiver or legal representative responsible for administering the drug and recording the time.

Exclusion Criteria:

• Exposure to an experimental drug, experimental biologic or experimental medical device within the longer of 5 half-lives or 3 months before screening

• Residence in a skilled nursing facility

• Clinically significant laboratory test results

• Clinically significant untreated hypothyroidism (if treated, thyroid-stimulating hormone level and thyroid supplementation dose must be stable for at least 6 months before screening)

• Insufficiently controlled diabetes mellitus or requiring insulin

• Renal insufficiency (serum creatinine >2.0 mg/dL)

• Malignant tumor within 3 years before screening (except squamous and basal cell carcinoma or cervical carcinoma in situ or localized prostate cancer or localized stage 1 bladder cancer)

• History of ischemic colitis or ischemic enterocolitis

• Unstable medical condition that is clinically significant in the judgment of the investigator

• Alanine transaminase (ALT) or aspartate transaminase (AST) >2 times the upper limit of normal or total bilirubin greater than the upper limit of normal.

• History of myocardial infarction or unstable angina within 6 months before screening

• History of more than 1 myocardial infarction within 5 years before screening

• Clinically significant cardiac arrhythmia (including atrial fibrillation), cardiomyopathy, or cardiac conduction defect (patients with a pacemaker are acceptable)

• Symptomatic hypotension, or uncontrolled hypertension

• Clinically significant abnormality on screening electrocardiogram (ECG), including but not necessarily limited to a confirmed corrected QT value >= 450 msec for males or >= 470 msec for females.

• Stroke within 18 months before screening, or history of a stroke concomitant with onset of dementia

• History of brain tumor or other clinically significant space-occupying lesion on CT or MRI

• Head trauma with clinically significant loss of consciousness within 12 months before screening or concurrent with the onset of dementia

• Onset of dementia secondary to cardiac arrest, surgery with general anesthesia, or resuscitation

• Specific degenerative CNS disease diagnosis other than Alzheimer's disease (eg, Huntington's disease, Creutzfeld-Jacob disease, Down's syndrome, Frontotemporal Dementia, Parkinson's disease)

• Wernicke's encephalopathy

• Active acute or chronic Central Nervous System infection

• Donepezil 23 mg or greater quaque die currently or within 3 months prior to enrollment in the study

• Discontinued AChEI < 30 days prior to enrollment in the study

• Antipsychotics; low doses are allowed only if given for sleep disturbances, agitation and/or aggression, and only if the subject has received a stable dose for at least 3 months before enrollment in the study

• Tricyclic antidepressants and monoamine oxidase inhibitors; all other antidepressants are allowed only if the subject has received a stable dose for at least 3 months before enrollment in the study

• Anxiolytics or sedative-hypnotics, including barbiturates (unless given in low doses for benign tremor); low doses of benzodiazepines and zolpidem are allowed only if given for insomnia/sleep disturbance, and only if the subject has received a stable dose for at least 3 months before enrollment in the study

• Peripherally acting drugs with effects on cholinergic transmission

• Immunosuppressants, including systemic corticosteroids, if taken in clinically immunosuppressive doses (Steroid use for allergy or other inflammation is permitted.)

• Antiepileptic medications if taken for control of seizures

• Chronic intake of opioid-containing analgesics

• Sedating H1 antihistamines

• Nicotine therapy (all dosage forms including a patch), varenicline (Chantix), or similar therapeutic agent within 30 days before screening

• Clinically significant illness within 30 days of enrollment

• History of significant neurological, hepatic, renal, endocrine, cardiovascular, gastrointestinal, pulmonary, or metabolic disease

• Positive serum hepatitis B surface antigen (HBsAg) or positive hepatitis C virus (HCV) antibody test at screening

• Positive HIV test at screening

• Loss of a significant volume of blood (> 450 mL) within 4 weeks prior to the study

• Metformin or cimetidine.